The Protective Role Of Mitochondrial ATP Sensitive Potassium Channels Opener Postconditioning In Rat’s Lung Ischemia/Reperfusion Injury

Background:With the development of the cardiopulmonary bypass (CPB) and clinicalapplications,it make the heart surgery possiblely and bring the Gospel to a lot of heart patients.Butthe the incidence of complications,especially the complications of lung.after CPB is stillhigh.Postoperative pulmonary dysfunction caused by CPB has become the main cause of death inpatients.The pulmonary dysfunction after CPB is mainly caused by lung ischemia-reperfusioninjury (LIRI).As for ischemia-reperfusion injury (I/R) research in-depth,Scholars found thatischemic postconditioning (IPO) on ischemia-reperfusion injury of organs had important protectiveeffect, and had the advantages which ischemic preconditioning (IPC) didn’t have.After the scholarsputsing forward the concept of drug post-processing, it make people have further understanding totreat organs of I/R by IPO.In recent years, studies have shown that the ultimate targets of IPO ismitochondrial ATP sensitive potassium channel (mitoKATP) which plays an important role in theprocess iof the I/R.As a kind of specificity activators of mitoKATP, nicorandilcan activat themitoKATPto protect cells.Objective: To discuss the function and possible mechanism of Nicorandil IPO in themitigation of rat’s Lung ischemia-reperfusion injury(LIRI) as mitoKATPopener.Methods：The model of rat’s LIRI was established.50rats were averagely divided intofive groups at random: sham operation group, IRI group, IPO group, Nicorandil(Nic)group and combination group of Nicorandil and5-hydroxydecanoate.The level ofmalondialdehyde(MDA), superoxide Dismutase(SOD), the ratio of W/D were tested ineach group. Meanwhile, lung tissue cell apoptotic index(AI) was tested withTdT-mediated dUTP-biotin nick end labeling(TUNEL) and the expression level ofcaspase-3in lung tissue was determined with Immunohistochemistry staining. Lungpathomorphological observation was performed with Light and electron microscope. Results：The level of MDA, AI, ratio of W/D, and expression of caspase-3wereincreased significantly, while the activity of SOD was decreased in IRI andcombination group of Nicorandil and5-hydroxydecanoate, compared with shamgroup(P<0.05); but the opposite situation was observed when compared with IPO andNic groups(P<0.05); no significant difference was found between IRI and combinationgroup of Nicorandil and5-hydroxydecanoate, the same result was shown between IPOand Nic groups.Conclusion;LIRI was alleviated by Nicorandil through simulating IPO protectivemechanism, which may include opened mitoKATP, decreased MDA, increased SODand downregulated caspase-3.